Phase II Dutasteride in combination with CAB vs CAB in SDC (DUCT)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Stichting Radboud University Medical Center

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

20 Sep 2022 → ongoing

Decision date (initial)

2022-08-11

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Radboudumc · ZonMw

External identifiers

EU CT number

2022-500745-24-00

ClinicalTrials.gov

NCT05513365

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To determine the efficacy of dutasteride in combination with combined androgen blockade therapy in patients with recurrent and/or metastatic salivary duct carcinoma

Secondary objectives 5

1. To assess other indicators of therapy efficacy
2. To assess the safety profile of dutasteride when combined with combined androgen blockade therapy
3. To assess the quality of life of patients treated with dutasteride in combination to combined androgen blockade therapy
4. To explore predictive markers of response
5. To assess the expression of molecular targets and to document the modulation of response in the tumor microenvironment

Conditions and MedDRA coding

Salivary Duct Carcinoma

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Pathologically/histologically proven diagnosis of (incurable) AR+ R/M salivary duct carcinoma
2. AR positive diseases (strong expression in at least 1% of nuclei of neoplastic cells based on central IHC review)
3. Measurable disease per RECIST version 1.1 at baseline
4. Age ≥ 18 years
5. Written informed consent must be given according to national/local regulation
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
7. Adequate bone marrow function: (WBC ≥ 3.5x10^9 /L; Absolute neutrophil count (ANC) ≥ 1.5x10^9/L; Hemoglobin ≥ 6.20 mmol/L; Platelet count ≥ 100x10^9/L)
8. Adequate liver function: (Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times upper limit of normal (ULN) OR ≤ 5.0 times ULN for patients with liver metastases; Bilirubin ≤ 1.5 times ULN. For patients known with Gilbert’s Syndrome ≤ 3.0 times ULN is permitted)
9. Adequate renal function: (Serum creatinine level ≤ 1.5 times ULN or calculated creatinine clearance ≥ 30 mL/min based on CKD-EPI-GFR)
10. Adequate cardiac function

Exclusion criteria 12

1. Patients with history of allergic reactions attributed to compounds of similar chemical or biological composition to goserelin, bicalutamide or dutasteride
2. Patients with peanut or soy allergy (dutasteride capsules contain lecithin which may contain soy oil)
3. Patients who do not have adequate swallowing capacity
4. Patients familiar with Long QT-syndrome (LQTS)
5. Patients (M/F) with reproductive potential not implementing adequate contraceptive measures
6. Patients that are pregnant or lactating
7. Patients with uncontrolled illness including: Cardiovascular disorders, including symptomatic congestive heart failure, unstable angina pectoris, or serious cardiac arrhythmias; Uncontrolled hypertension (defined as sustained systolic BP > 160 mm Hg, or diastolic BP > 100 mm Hg. Unless evidence of white-coat hypertension), Stroke (including TIA), myocardial infarction, or other ischemic event within 6 months before inclusion; Serious active infections .
8. Concomitant (or within 4 weeks before inclusion) administration of any other experimental drug under investigation
9. Concomitant (or within 6 months before inclusion) administration of any 5-alpha reductase inhibitor, i.e. dutasteride or finasteride
10. Concurrent treatment with any other anti-cancer therapy within the last 4 weeks before inclusion
11. Curative radiation therapy within the last 4 weeks before inclusion or palliative radiation therapy 1 week before start of study
12. Any condition which, in the opinion of the investigator, would preclude participation in this clinical study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Overall response rate (ORR) defined as proportion of participants who have a confirmed complete response (CR) or partial response (PR) determined by Investigator according to RECIST v1.1
2. Duration of Response (DoR), defined as the time from first tumor assessment at which the overall response was recorded as PR or CR that is subsequently confirmed until documented progressive disease (PD) determined by Investigator per RECIST v1.1 or death from any cause, whichever occurs first

Secondary endpoints 8

1. Progression free survival (PFS), defined as the time from study enrolment until the date of first documented disease progression by Investigator as per RECIST v1.1, or death due to any cause, whichever occurs first
2. Overall survival (OS), defined as the time from study enrolment to the date of death due to any cause
3. Clinical benefit rate (CBR) including confirmed CR or PR at any time or stable disease (SD) of at least 6 months determined by Investigator as per RECIST v1.1
4. Incidence of SAE’s according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
5. Quality of life (QoL) assessments according to approved EORTC (QLQ-C30, QLQ-H&N35, QLQ-SHQ22) and VAS questionnaires
6. Circulating tumor DNA (ctDNA) and serum testosterone
7. AR, AR splice variants and SRD5A1/SRD5A2 mRNA expression on baseline and post-treatment tumor tissue samples
8. Various subsets of immune cells. Including different panels, but not limited to, a lymphocyte panel, a dendritic cell panel, a checkpoint panel, and a myeloid-derived suppressor cell panel

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Stichting Radboud University Medical Center

Sponsor organisation

Stichting Radboud University Medical Center

Address

Geert Grooteplein Zuid 10

City

Nijmegen

Postcode

6525 GA

Country

Netherlands

Scientific contact point

Organisation

Stichting Radboud University Medical Center

Contact name

RTC clincial studies

Public contact point

Organisation

Stichting Radboud University Medical Center

Contact name

RTC clincial studies

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

2 submissions — initial application plus substantial / non-substantial modifications